MEDizzy - A 50-year-old obese female with a 5-year history of mild

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Disorders of the Kidney and Urinary Tract

A 50-year-old obese female with a 5-year history of mild hypertension controlled by a thiazide diuretic is being evaluated because proteinuria was noted on a urine dipstick during her routine yearly medical visit. Physical examination discloses a height of 167.6 cm (66 in), weight of 91 kg (202 lb), blood pressure of 130/80 mmHg, elevated jugular venous pressure, a fourth heart sound, and trace pedal edema. Laboratory values are as follows: Serum creatinine: 106 μmol/L (1.2 mg/dL), BUN: 6.4 mmol/L (18 mg/dL), Creatinine clearance: 87 mL/min, Urinalysis: pH 5.0; specific gravity 1.018; protein 3+; no glucose; occasional coarse granular cast Urine protein excretion: 5.9 g/d. A renal biopsy demonstrates that 60% of the glomeruli, mostly in the corticomedullary junction, have segmental scarring by light microscopy, with the remainder of the glomeruli appearing unremarkable. What is the most likely diagnosis?

ExplanationFocal segmental glomerulosclerosis (FSGS) refers to a pattern of renal injury characterized by segmental glomerular scars that involve some but not all glomeruli; the clinical findings of FSGS largely manifest as proteinuria. When the secondary causes of FSGS are eliminated, the remaining patients are considered to have primary FSGS. Secondary causes of FSGS include viral infection (human immunodeficiency virus (HIV), hepatitis B, parvovirus), hypertensive nephropathy, reflux nephropathy, cholesterol emboli, drugs (heroin, analgesics, pamidronate), oligomeganephronia, renal dysgenesis, Alport syndrome, sickle cell disease, lymphoma, radiation nephritis, and a number of familial podocytopathies. The incidence of FSGS is increasing, and it now represents up to one-third of cases of nephrotic syndrome in adults and one-half of cases of nephrotic syndrome in African cases of nephrotic syndrome in adults and one-half of cases of nephrotic syndrome in African Americans, in whom it is seen more commonly. FSGS can present with hematuria, hypertension, any level of proteinuria, or renal insufficiency. Nephrotic-range proteinuria, African American race, and renal insufficiency are associated with a poor outcomes, with 50% of patients reaching renal failure in 6–8 years. FSGS rarely remits spontaneously, but treatment-induced remission of proteinuria significantly improves prognosis. Treatment of patients with primary FSGS should include inhibitors of the renin-angiotensin system. The treatment of secondary FSGS typically involves treating the underlying cause and controlling proteinuria. There is no role for steroids or other immunosuppressive agents in secondary FSGS. Hypertensive nephrosclerosis exhibits more prominent vascular changes and patchy, ischemic, totally sclerosed glomeruli. In addition, nephrosclerosis seldom is associated with nephrotic-range proteinuria. Minimal change disease usually is associated with symptomatic edema and normal-appearing glomeruli as demonstrated on light microscopy. This patient’s presentation is consistent with that of membranous nephropathy, but the biopsy is not. With membranous glomerular nephritis, all glomeruli are uniformly involved with subepithelial dense deposits. There are no features of crescentic glomerulonephritis present. The characteristic pattern of focal (not all glomeruli) and segmental (not the entire glomerulus) glomerular scarring is shown in the figure. The history and laboratory features are also consistent with this lesion: some associated hypertension, diminution in creatinine clearance, and relatively inactive urine sediment. The “nephropathy of obesity” may be associated with this lesion secondary to hyperfiltration; this condition may be more likely to occur in obese patients with hypoxemia, obstructive sleep apnea, and right-sided heart failure.